The latest medical research on Immunology & Allergy

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about immunology & allergy gathered by our medical AI research bot.

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Reaching the second 90: the strategies for linkage to care and antiretroviral therapy initiation.

Current Opinion in Cell Biology

We present recent literature describing interventions for linkage to HIV care in the era of Universal Test and Treat (UTT) policies. We also provide information for ongoing studies of linkage to care strategies registered with ClinicalTrials.gov.

Differentiated service delivery for linkage to care involves implementing strategies that simplify and adapt HIV services to better serve individual needs and reduce unnecessary burdens on the health system. Recent strategies have focused not only on clinic-based populations testing for HIV but also emphasize community-based services and HIV self-testing, which create different challenges for linkage to the healthcare system. Some recent developments in linkage to care strategies include: case management, care integration with other desirable health services, financial incentives, home-based, and peer-led services. The demonstrated strategies have varying levels of success and engagement in care; further work is needed to address ongoing barriers in HIV care.

Progress towards meeting the 90-90-90 benchmarks has left gaps in linkage to care that require care-system development to facilitate increased access to care under UTT policies. Most notably, new strategies will need to focus on addressing the distinct needs of key populations and bolstering linkage to care from community-based and self-testing services.

Distinct inflammatory profiles in HIV-infected individuals under ART using cannabis, cocaine or cannabis plus cocaine.

AIDS

To evaluate the effects of cannabis and/or cocaine use on inflammatory, oxidative stress status and circulating monocyte subsets in HIV-infected individuals under antiretroviral therapy.

sCD14, IFABP, TNF-α, IL-6, IL-8 and IL-10 levels were evaluated using ELISA, CRP by turbidimetry; lipid peroxidation (TBARS) spectrofluometrically and total thiol levels by using 5-5'-dithio-bis (2-nitrobenzoic acid) reagent. Monocyte subsets and activation were assessed by flow cytometry.

All HIV-infected drug user groups showed higher sCD14 levels compared to HIV+ non-drug users. IFABP was increased in HIV+ drug-users in relation to healthy individuals. Cannabis use lowered the percentages of inflammatory, non-classical, activated-classic, and activated-inflammatory monocytes. Cocaine users showed increased plasmatic TNF-α and TBARS levels, decreased thiols content and lower activated-classic and inflammatory-monocyte percentages. Cannabis-plus-cocaine use increased CRP, IL-8 and IL-6/IL-10 ratio, but decreased thiols content, and inflammatory and activated-classic monocyte percentages. PBMCs of cannabis and cannabis-plus-cocaine users showed low potential cytokine production either spontaneously or under LPS-stimulation.

In HIV infection the use of cannabis induces predominantly an anti-inflammatory profile. The use of cocaine and cannabis-plus-cocaine showed a mixed pro- and anti-inflammatory profile, with predominance of inflammatory status. Further studies are required to better understand the action of these drugs in HIV infection.

Long-term evolution of transmitted CXCR4-using HIV-1 under effective antiretroviral therapy.

AIDS

To study the long-term evolution of the transmitted CXCR4-using viruses. CCR5-using viruses (R5 viruses) predominate during primary HIV-1 infections (PHI) while CXCR4-using viruses are isolated in less than 10% of PHI.

We used MiSeq ultra-deep sequencing to determine the composition of the virus quasispecies during PHI and at the end of follow-up (median time of follow-up: 12.5 years).

X4 viruses were detected by genetic analysis in 3/6 samples from the R5X4 group, accounting for 1.3-100% of the virus quasispecies, during PHI, and in 4/6 samples (accounting for 6.7-100%) at the end of follow-up. No X4 virus was detected in the R5 group during PHI and in only one patient (accounting for 1.2%) at the end of follow-up. The complexity of the virus quasispecies at the stage of PHI was higher in the R5X4 group than in the R5 group. Complexity increased from PHI to the end of follow-up in the R5 group but remained stable in the R5X4 group.

CXCR4-using viruses persisted in the PBMCs of several patients on suppressive antiretroviral therapy for a median duration of 12.5 years after PHI. The genetic complexity of HIV-1 evolved differently post-PHI in patients infected with R5X4 viruses from those infected with R5 viruses.

Double dissociation of HIV and substance use disorders effects on neurocognitive tasks dependent on striatal integrity.

AIDS

Substance use is common among individuals infected with HIV, yet whether neurocognitive effects of HIV can be distinguished from more nonspecific effects of drug dependence and associated comorbidities is not known.

We compared the performance of 458 (31% HIV-infected) substance dependent individuals (SDIs) and 90 individuals (23% HIV-infected) with no history of substance use disorders (SUDs) on measures of delay discounting and probability learning, tasks which are differentially sensitive to addictive processes and HIV serostatus, respectively.

In factorial analyses of covariance adjusted for age, years of education, and sex, we found that SDIs showed significantly higher rates of delay discounting, regardless of HIV serostatus (P < .05). Conversely, HIV-infected individuals performed significantly more poorly on probability learning compared with uninfected groups, regardless of SUD history (P < .05).

Theory-driven cognitive neuropsychological tasks may have the capacity to detect neurocognitive effects of HIV not attributable solely to substance use; evidence from functional neuroimaging studies with more selective neurocognitive probes will be critical for hypothesis testing and mapping underlying brain systems more precisely.

Universal health coverage and key populations.

Current Opinion in Cell Biology

There is renewed focus at global and national level to adopt commitments to ensure universal access to health services. The present study highlights key considerations to ensure that the commitment to 'leave no one behind' includes key populations, recognizing the specific impact of marginalization, stigma, discrimination, and criminalization on their access to health.

Universal health coverage (UHC) means that all people can use the promotive, preventive, curative, rehabilitative, and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship. Countries commit to UHC through Sustainable Development Goals (SDG Target 3.8 Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to well tolerated, effective, quality, and affordable essential medicines).

UHC cannot be achieved without addressing the needs of key populations. At the same time, the goal of UHC provides new opportunities to improve health equity and the health of key populations. Political commitment, defining and including essential high-impact, evidence-based interventions for key populations, and their full integration into national health benefit packages; integrated, decentralized, and differentiated health services with involvement, ownership, and acceptance of communities to ensure equity and quality; ensuring financing for UHC provides coverage for key populations, including those who may be undocumented, are needed. Developing more effective interventions and service delivery approaches, providing a supportive policy and legal environment; and measuring progress against clear targets for accountability and programme adjustment will also be required for key populations to benefit fully from UHC.

Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience on behalf of the French CANCERVIH network.

AIDS

To report efficacy and tolerance of nivolumab or pembrolizumab, PD-1 inhibitors, in people living with HIV (PLWHIV) and cancer.

From May 2014 to January 2019, 575 HIV infected patients have been discussed in the French CANCERVIH national multidisciplinary board and included in the network database. 23 patients were treated with ICI in daily practice. We report the demographic characteristics, CD4 T cell counts, HIV viral loads, safety and efficacy data of these 23 PLWHIV treated in routine practice with nivolumab or pembrolizumab for non-small cell lung cancer (n = 21), melanoma (n = 1) and head and neck cancer (n = 1) retrospectively collected from the database CANCERVIH network. The median CD4 T cell count at treatment initiation was 370/mm (IQR: 125-1485). HIV viral load was undetectable in all patients.

As of 29 April 2019, with a median follow-up of 10.8 months (2.0-27.7), the median number of injections was 6 (IQR: 4-18). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 23 patients, a partial response was observed in 5 patients (22%), a stabilization for 5 (22%) and a progression in 13 (57%). Only one patient experienced a positive HIV viral load, but this occurred following ART interruption.

Treatment with PD-1 inhibitors seems to have an efficacy signal and be well tolerated in PLWHIV, including impact on CD4 lymphocyte count and HIV load, that should be monitored during treatment course (regarding real-life experience).

Comprehensive HIV risk reduction interventions for 2020 and beyond: product choices and effective service-delivery platforms for individual needs and population-level impact.

Current Opinion in Cell Biology

This review summarizes key HIV prevention strategies in the 2020 toolkit and discusses opportunities to maximize the public health impact of these prevention interventions at a population level.

HIV prevention has relied on counseling, HIV testing, and condom distribution for the past three decades. Recent exciting work has provided evidence on effective HIV prevention interventions, including antiretroviral therapy for HIV prevention, expanding preexposure prophylaxis modalities, and voluntary medical male circumcision which all reduce individual-level HIV risk. Efficient service-delivery approaches are necessary to deliver these products at scale while addressing population-specific needs. These approaches include: making it easier to get individuals HIV tested and linked to prevention services; de-medicalization to increase access to prevention products; creating welcoming clinic service-delivery environments; and integrating HIV prevention products into existing clinical platforms to support ongoing care engagement.

The 2020 HIV prevention toolkit includes powerful HIV prevention options, and product choice will be increasingly imperative. Meeting ambitious global HIV reduction targets in the next decade will require improved service-delivery platforms to get prevention choices to persons at risk while layering prevention coverage to achieve population-level impact.

Coronary atherosclerosis characteristics in HIV infected patients on long term antiretroviral therapy: insights from coronary computed tomography angiography.

AIDS

The aim of the study was to assess coronary artery disease (CAD) characteristics by coronary CT-angiography (CCTA) in individuals with HIV-infection on long-term antiretroviral therapy (ART) DESIGN:: Retrospective case-controlled matched cohort study METHODS:: 69 HIV positive patients who underwent 128-slice dual source CCTA (mean age 54.9 years, 26.1% females) with mean 17.8 ± 9.4 years of HIV-infection and a mean duration on ART of 13 ± 7.3 years were propensity score matched (1:1) for age, gender, BMI, and 5 cardiovascular risk factors with 69 controls.CCTA was evaluated for: stenosis severity (according to Coronary Artery Disease - Reporting and Data System (CAD-RADS)), total plaque burden (segment involvement score (SIS) and mixed-non-calcified plaque burden (G-score). As inflammatory biomarkers, high-risk-plaque (HRP) features (napkin-ring-sign, low-attenuation-plaque, spotty calcification, positive remodeling), perivascular fat attenuation index (FAI), and ectatic coronary arteries were assessed.

CAD-RADS was higher in HIV-positive participants as compared to controls (2.21 ± 1.4 vs 1.69 ± 1.5, p = 0.031). A higher prevalence of CAD and G-score (p = 0.043 and p = 0.003) was found.HRP prevalence (23 (34.3%) vs 8 (12.1%); p = 0.002) and the number of HRP (36 vs 10, p < 0.001) were higher in HIV-positive individuals. A perivascular FAI >-70 HU was present in 27.8% of HRP. Ectatic coronary arteries were found in 10 (14.5%) HIV-positive persons vs 0% in controls (p = 0.003).

Non-calcified and HRP burden in HIV-infected individuals on long-term ART is higher and associated with higher cardiovascular risk. Moreover, HIV-positive individuals displayed a higher stenosis severity (CAD-RADS) and more ectatic coronary arteries compared to the control group.

Getting to grips with the HIV epidemic in Russia.

Current Opinion in Cell Biology

In contrast to global patterns, the HIV epidemic in the Russian Federation continues to expand. The epidemic remains largely concentrated among key populations and their sexual partners but has the potential of affecting the general population. We have focused our analysis on legislative, policy-related, structural, and cultural obstacles that the country faces in confronting its epidemic.

The Russian Federation has the largest HIV epidemic in Europe. Recent epidemiological analyses have shown a decrease in the annual growth of new reported infections. However, stigma and discrimination, marginalization, legislative provisions, harsh policing, and the lack of relevant prevention programs remain compounding factors that limit access of at-risk populations to information, prevention, and care, including to treatment for a number of people who would know their serological status.

The ability of the Russian Federation to address the challenges it faces in dealing with a concentrated epidemic, will determine the future of the epidemic in the country.

The antagonism of folate receptor by dolutegravir: developmental toxicity reduction by supplemental folic acid.

AIDS

Maternal folate (vitamin B9) status is the largest known modifier of neural tube defect (NTD) risk, so we evaluated folate-related mechanisms of action for dolutegravir (DTG) developmental toxicity.

FOLR1 competitive binding studies were used to test DTG for FOLR1 antagonism. Human placenta cell line studies were used to test interactions with DTG, folate, and cations. Zebrafish were selected as an animal model to examine DTG-induced developmental toxicity and rescue strategies.

FOLR1 binding studies indicate DTG is a non-competitive FOLR1 antagonist at therapeutic concentrations. In vitro testing indicates calcium (2 mM) increases FOLR1-folate interactions and alters DTG-FOLR1-folate interactions and cytotoxicity. DTG does not inhibit downstream folate metabolism by dihydrofolate reductase (DHFR). Early embryonic exposure to DTG is developmentally toxic in zebrafish, and supplemental folic acid can mitigate DTG developmental toxicity.

Folates and FOLR1 are established modifiers of risk for NTDs, and binding data indicates DTG is a partial antagonist of FOLR1. Supplemental folate can ameliorate increased developmental toxicity due to DTG in zebrafish. The results from these studies are expected to inform and guide future animal models and clinical studies of DTG-based ART in women of childbearing age.

Homelessness at diagnosis is associated with death among people with HIV in a population-based study of a U.S. City.

AIDS

San Francisco (SF), California, has experienced a 44% reduction in new HIV diagnoses since 2013 supported by its "Getting to Zero" initiative; however, the age-adjusted mortality rate in people with HIV (PWH) has not decreased. We sought to identify factors associated with death among PWH in SF.

Among PWH in the SF HIV surveillance registry, a random sample of 48 decedents from July 1, 2016 to May 31, 2017 were each matched to 2-3 controls who were alive at the date of death (108 controls matched on age and time since diagnosis). Covariates included demographics, substance use, housing status, medical conditions, and care indicators from the study population. We used matched-pair conditional logistic regression to examine factors associated with mortality.

Of the 156 PWH in the study, 14% were African-American, 14% Latino, and 8% female sex. In adjusted analysis, factors associated with higher odds of death included: homelessness at HIV diagnosis [adjusted odds ratio (AOR) = 27.4 95% confidence interval (CI) = 3.0-552.1], prior-year injection drug use (AOR = 10.2 95% CI = 1.7-128.5), prior-year tobacco use (AOR = 7.2 95% CI = 1.7-46.9), being off ART at any point in the prior year (AOR = 6.8; 95% CI = 1.1-71.4), and being unpartnered vs. married/partnered (AOR = 4.7; 95% CI = 1.3-22.0).

People homeless at HIV diagnosis had 27-fold higher odds of death compared to those with housing; substance use and retention on ART in the prior year are other important intervenable factors. New strategies to address these barriers, and continued investment in supportive housing and substance use treatment, are needed.

Risk factors and impact of patterns of co-occurring comorbidities in people living with HIV.

AIDS

To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes.

Common patters of comorbidities in PLWH participating in the POPPY study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns' severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner (GP) visits using Poisson regression.

1073 PLWH were analysed: 85.2% male, median (IQR) age 52 (47-59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases (CVD), mental health problems, metabolic disorders and chest/other infections (all p's≤0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (p < 0.001). CVD was associated with poorer physical health (p = 0.02), higher risk of functional impairment (p = 0.02) and hospitalization (p < 0.001) and with higher number of GP visits (p < 0.001). Severity of mental health (all p's < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes.

Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.